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Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice

Fig 4

Mice with a hepatocyte-specific IFNAR deletion succumb to CVB3 infection and show ubiquitous virus dissemination.

C57BL/6 (black), IFNAR-/- (white), Alb-Cre+/-IFNARfl/fl (red), and LysM-Cre+/-IFNARfl/fl (blue) mice were infected i.p with 2 × 104 PFU CVB3 and (A) monitored for survival. Mice that showed severe clinical symptoms or more than 20% body weight lost were sacrificed (n = 9–16). Differences between the groups were determined using log-rank statistics. (B) Alanine aminotransferase (ALT) or lipase levels were determined from serum at the indicated dpi. Of note, for Alb-Cre+/-IFNARfl/fl mice values at 4 and 5 dpi from only one surviving mouse per day are depicted. Values are mean ± SEM (n = 3–13). For statistical analysis, IFNAR-/-, Alb-Cre+/-IFNARfl/fl, or LysM-Cre+/-IFNARfl/fl mice were compared with C57BL/6 mice by One-Way ANOVA test. (C) Graphs depict virus titers in liver, pancreas, spleen, heart, salivary gland (SG), and brain based on plaque formation 3 dpi (n = 2–5). Bars depict mean. Mann-Whitney test was used for statistical analysis, *P < 0.05; **P < 0.01. ***P < 0.001.

Fig 4

doi: https://doi.org/10.1371/journal.ppat.1007235.g004